Participation of the miR-22-HDAC4-DLCO Axis in Patients with COPD by Tobacco and Biomass

Biomolecules. 2019 Dec 6;9(12):837. doi: 10.3390/biom9120837.

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and systemic inflammation. The main causes of COPD include interaction between genetic and environmental factors associated with tobacco smoking (COPD-TS) and/or exposure to biomass smoke (COPD-BS). Several microRNAs (miRNAs) control posttranscriptional regulation of COPD-TS associated gene expression. The miR-22-HDAC4-IL-17 axis was recently characterized. It is still unknown, however, whether this axis, participates in COPD-BS. To investigate, 50 patients diagnosed with severe-to-very severe COPD GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages III/IV, were recruited, 25 women had COPD-BS (never smokers, exposed heavily to BS) and 25 had COPD-TS. Serum levels of miRNA-22-3p were measured by RT (Reverse Transcription)-qPCR, while the concentration of HDAC4 (Histone deacetylase 4) was detected by ELISA. Additionally, we looked for association between serum HDAC4 and DLCOsb (Single-breath diffusing capacity of the lung for carbon monoxide), as % of predicted by age, height, and gender, one of the main differences described between COPD-BS and COPD-TS. Women with COPD-BS were older and shorter and had a higher DLCOsb %P (percent predicted) compared to COPD-TS. Serum miR-22-3p was downregulated in COPD-BS relative to COPD-TS. In contrast, the concentration of HDAC4 was higher in COPD-BS compared to COPD-TS. Furthermore, a positive correlation between serum HDAC4 levels and DLCOsb %P was observed. We concluded that the miR-22-HDAC4-DLCO axis behaves differently in patients with COPD-BS and COPD-TS.

Keywords: biomass smoke; copd; dlco; hdac4; mir-22; tobacco smoking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Histone Deacetylases / metabolism*
  • Humans
  • MicroRNAs* / metabolism
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Repressor Proteins / metabolism
  • Smoke / adverse effects
  • Smoking / adverse effects*
  • Tobacco Products
  • Tobacco Smoke Pollution / adverse effects*

Substances

  • MIRN22 microRNA, human
  • MicroRNAs
  • Repressor Proteins
  • Smoke
  • Tobacco Smoke Pollution
  • HDAC4 protein, human
  • Histone Deacetylases